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Designing and developing inhibitors against the epigenetic target DNA methyltransferase (DNMT) is an attractive strategy in epigenetic drug discovery. DNMT1 is one of the epigenetic enzymes with significant clinical relevance. Structure-based de novo design is a drug discovery strategy that was used in combination with similarity searching to identify a novel DNMT inhibitor with a novel chemical scaffold and warrants further exploration. This study aimed to continue exploring the potential of de novo design to build epigenetic-focused libraries targeted toward DNMT1. Herein, we report the results of an in-depth and critical comparison of ligand- and structure-based de novo design of screening libraries focused on DNMT1. The newly designed chemical libraries focused on DNMT1 are freely available on GitHub.
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DNA (Citosina-5-)-Metiltransferase 1 , Desenho de Fármacos , Inibidores Enzimáticos , Ligantes , DNA (Citosina-5-)-Metiltransferase 1/antagonistas & inibidores , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Humanos , Bibliotecas de Moléculas Pequenas/farmacologia , Bibliotecas de Moléculas Pequenas/química , Relação Estrutura-AtividadeRESUMO
BACKGROUND: Fleck corneal dystrophy (FCD) is a rare autosomal dominant disease that affects exclusively the corneal stroma. The disease is caused by heterozygous variants in PIKFYVE, a gene encoding a lipid kinase involved in multiple cellular pathways, primarily participating in membrane dynamics and signaling. This report describes a familial case of FCD caused by a complete deletion of the PIKFYVE gene. MATERIAL AND METHODS: A clinical ophthalmic examination was performed on the proband and family members. Genetic testing included next-generation sequencing (multigene panel), and chromosomal microarray analysis. A quantitative PCR assay was designed in order to segregate the deletion. RESULTS: A 19-year-old male, with no family or personal history of ocular disease, presented for evaluation due to an acute illness consisting of burning, foreign body sensation, and red eye. Slit lamp biomicroscopy revealed bilateral small pterygia and scattered bilateral white opacities in the corneal stroma, a very similar corneal phenotype was found in the 47-year-old father, who was asymptomatic. NGS detected a heterozygous deletion of the entire PIKFYVE coding sequence. CMA in DNA from the propositus indicated a 543 kb deletion in 2q33.3q34 spanning the entire PIKFYVE gene. The deletion was confirmed in the father. CONCLUSIONS: We add to the molecular spectrum of FCD by describing a familial case of a whole PIKFYVE gene deletion in affected subjects. Our findings support that normal expression of PIKFYVE is necessary for corneal keratocytes homeostasis and normal corneal appearance. We conclude that PIKFYVE haploinsufficiency is the molecular mechanism underlying this familial case of FCD.
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Distrofias Hereditárias da Córnea , Linhagem , Fosfatidilinositol 3-Quinases , Humanos , Masculino , Adulto Jovem , Distrofias Hereditárias da Córnea/genética , Distrofias Hereditárias da Córnea/diagnóstico , Fosfatidilinositol 3-Quinases/genética , Pessoa de Meia-Idade , Deleção de Genes , Feminino , Adulto , Deleção de Sequência , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
Wheat germ agglutinin (WGA) demonstrates potential as an oral delivery agent owing to its selective binding to carbohydrates and its capacity to traverse biological membranes. In this study, we employed differential scanning calorimetry and molecular dynamics simulations to comprehensively characterize the thermal unfolding process of both the complete lectin and its four isolated domains. Furthermore, we present the nuclear magnetic resonance structures of three domains that were previously lacking experimental structures in their isolated forms. Our results provide a collective understanding of the energetic and structural factors governing the intricate unfolding mechanism of the complete agglutinin, shedding light on the specific role played by each domain in this process. The analysis revealed negligible interdomain cooperativity, highlighting instead significant coupling between dimer dissociation and the unfolding of the more labile domains. By comparing the dominant interactions, we rationalized the stability differences among the domains. Understanding the structural stability of WGA opens avenues for enhanced drug delivery strategies, underscoring its potential as a promising carrier throughout the gastrointestinal environment.
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Estabilidade Proteica , Aglutininas do Germe de Trigo , Varredura Diferencial de Calorimetria , Simulação de Dinâmica Molecular , Ressonância Magnética Nuclear Biomolecular , Domínios Proteicos , Aglutininas do Germe de Trigo/químicaRESUMO
Neurotrophic keratopathy is an uncommon degenerative corneal disorder characterized by compromised corneal sensory innervation resulting in the formation of epithelial defects and nonhealing corneal ulcers. Various treatment modalities are available to stabilize disease progression, improve patient well-being, and prevent vision loss. For eligible patients, medical and surgical reinnervation have emerged as pioneering therapies, holding promise for better management. We present a comprehensive review of the disorder, providing an update relevant to ophthalmologists on pathogenesis, diagnosis, treatment options, and novel therapies targeting pathophysiological pathways.
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Córnea , Humanos , Córnea/inervação , Doenças da Córnea/terapia , Doenças da Córnea/diagnóstico , Doenças da Córnea/fisiopatologia , Doenças da Córnea/etiologiaRESUMO
BACKGROUND: Developing effective vaccines against SARS-CoV-2 that consider manufacturing limitations, equitable access, and acceptance is necessary for developing platforms to produce antigens that can be efficiently presented for generating neutralizing antibodies and as a model for new vaccines. RESULTS: This work presents the development of an applicable technology through the oral administration of the SARS-CoV-2 RBD antigen fused with a peptide to improve its antigenic presentation. We focused on the development and production of the recombinant receptor binding domain (RBD) produced in E. coli modified with the addition of amino acids extension designed to improve antigen presentation. The production was carried out in shake flask and bioreactor cultures, obtaining around 200 mg/L of the antigen. The peptide-fused RBD and peptide-free RBD proteins were characterized and compared using SDS-PAGE gel, high-performance chromatography, and circular dichroism. The peptide-fused RBD was formulated in an oil-in-water emulsion for oral mice immunization. The peptide-fused RBD, compared to RBD, induced robust IgG production in mice, capable of recognizing the recombinant RBD in Enzyme-linked immunosorbent assays. In addition, the peptide-fused RBD generated neutralizing antibodies in the sera of the dosed mice. The formulation showed no reactive episodes and no changes in temperature or vomiting. CONCLUSIONS: Our study demonstrated the effectiveness of the designed peptide added to the RBD to improve antigen immunostimulation by oral administration.
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COVID-19 , SARS-CoV-2 , Animais , Humanos , Camundongos , Adjuvantes Imunológicos , Vacinas contra COVID-19 , Escherichia coli , Administração Oral , Antígenos Virais , Anticorpos Neutralizantes , Peptídeos , Anticorpos AntiviraisRESUMO
Purpose: To evaluate the risk factors associated with diabetic macular edema (DME) in patients with a recent type 2 diabetes mellitus (T2DM) diagnosis. Patients and Methods: We conducted a case-control study at a third-level hospital in Mexico City. We enrolled patients ≥18 years old, with T2DM less than five years of diagnosis, without disabling complications, and non-smokers. The control group was patients with diabetic retinopathy and without macular edema (DR-DME). Cases were patients with DR+DME. We measured fasting glucose, creatinine, lipid profile, urinary albumin/creatinine ratio (ACR), and HbA1c. An ophthalmological examination consisted of visual acuity measurement, digital three-field fundus photography with an automatic non-mydriatic camera, slit lamp, and Optical coherence tomography (OCT) examination. Results: 183 and 61 patients with DR-DME and DR+DME, respectively, were included in the analysis. The prevalence of mild DR was higher in the DR-DME group, but the frequencies of moderate and severe retinopathy were higher in the DR+DME group. Patients in the DR-DME group had better vision than those in the DR+DME group. Logistic regression analysis revealed that age (OR, 1.07), HbA1c (OR, 1.19), and Albumin-to-Creatinine Ratio (ACR) > 30 mg/g (OR, 3.37) were associated with an increased possibility of DME compared to DR-DME. Conclusion: Our study provides insights into the association between risk factors and DME. We found a statistically strong association between HbA1c levels, age, and ACR. Patients with poor metabolic control should undergo an extensive medical examination to screen for DME, which may be related to the chronicity of DM and renal damage.
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OBJECTIVES: The aims of the study are to examine the perception of the human papillomavirus (HPV) vaccine among those with and without a history of cervical dysplasia and to examine perceptions of the vaccine for their children. MATERIALS AND METHODS: Patients were recruited to complete a survey about the HPV vaccine for both themselves and their children. Patients in a colposcopy clinic with a history of abnormal cervical cytology and patients in a benign gynecology clinic without a history of abnormal cervical cytology were recruited. Participants' medical records were reviewed. Demographics and survey answers were described, and Fisher exact test was used to compare the groups. RESULTS: One hundred eighty-three patients participated: 73 in colposcopy clinic and 110 in benign clinic. The majority self-identified as Black (74% colposcopy, 71% benign, p = .588) and reported an income less than $39,000 a year (77% colposcopy, 65% benign, p = .089). Fifty-six percent in benign clinic agreed the HPV vaccine is a good way to protect oneself from disease compared with 48% in colposcopy clinic ( p = .022). When examining results based on cytology, fewer patients in the highest-grade cytology group agreed the vaccine was effective (30% high-grade, 48% normal, 57% low-grade, p = .027) or a good way to protect themselves from disease (29% high-grade, 53% normal, 62% low-grade, p = .002). There was otherwise no statistically significant difference between the groups on questions regarding self or child vaccination. CONCLUSIONS: In a majority Black, low-income population, patients without a history of abnormal cervical cytology have more favorable perceptions of the HPV vaccine's effectiveness in preventing disease. Those with the highest-grade cytology had more negative perceptions of the vaccine's effectiveness and protectability.
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Infecções por Papillomavirus , Vacinas contra Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Criança , Gravidez , Humanos , Neoplasias do Colo do Útero/prevenção & controle , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/epidemiologia , Colposcopia , Papillomaviridae , Detecção Precoce de CâncerRESUMO
The study of corneal biomechanics has become relevant in recent years due to its possible applications in the diagnosis, management, and treatment of various diseases such as glaucoma, keratorefractive surgery and different corneal diseases. The clinical biomechanical investigation has become of great importance in the setting of refractive surgery to identify patients at higher risk of developing iatrogenic ectasia. This review focuses on two of the technologies available for clinical use, the Ocular Response Analyzer (Reichert Ophthalmic Instruments, Buffalo, NY, USA) and the Corvis ST (Oculus Optikgergäte GmbH, Wetzlar, Germany). Both are non-contact tonometers that provided a clinical evaluation of corneal biomechanics. The fundamentals and main parameters of each device are described, as well as their use in eye surgery and the corneal biomechanical behavior in eye diseases. Finally, we will discuss the more recent Brillouin microscopy biomechanical analysis, and the integration Scheimpflug-based corneal tomography and biomechanical data with artificial intelligence to increase accuracy to detect risk of ectasia.
El estudio de la biomecánica corneal ha cobrado relevancia en los últimos años debido a sus posibles aplicaciones en el diagnóstico, el manejo y el tratamiento de diversas enfermedades, como glaucoma, cirugía queratorrefractiva y diferentes enfermedades corneales. La investigación de la biomecánica corneal es de mucha importancia en el contexto de cirugía refractiva, pues podría identificar pacientes en riesgo de desarrollar una ectasia corneal iatrogénica. Esta revisión se centra en dos de las tecnologías disponibles para uso clínico: el Ocular Response Analyzer (Reichert Ophthalmic Instruments, Buffalo, NY, EE. UU.) y el Corvis ST (Oculus Optikgergäte GmbH, Wetzlar, Alemania). Ambos son tonómetros de no contacto que proporcionan una evaluación clínica de la biomecánica corneal. Se describen los fundamentos y los principales parámetros de cada dispositivo, así como su uso en cirugía ocular y el comportamiento biomecánico corneal en las enfermedades oculares. Finalmente, se mencionan los dispositivos más recientes de análisis biomecánico, como la microscopía de Brillouin, así como la integración de los datos biomecánicos y topográficos basados en Scheimpflug con la inteligencia artificial para aumentar la precisión en la detección del riesgo de ectasias.
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Inteligência Artificial , Glaucoma , Humanos , Fenômenos Biomecânicos , Dilatação Patológica , Córnea , Pressão IntraocularRESUMO
Cogan syndrome is a rare disease whose etiology is still undetermined. It typically affects men and women between the second and fourth decade of life. We report a case of Cogan syndrome with ocular and audio-vestibular involvement as a systemic manifestation in a 31-year-old woman.
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Síndrome de Cogan , Masculino , Humanos , Feminino , Adulto , Síndrome de Cogan/complicações , Síndrome de Cogan/diagnóstico , Diagnóstico DiferencialRESUMO
The aim of this study was to report a case with the use of amniotic membrane transplant and deep anterior keratoplasty in a patient with bilateral Acanthamoeba infectious keratitis as a treatment. A 20-year-old male presented with bilateral Acanthamoeba keratitis (AK) who was initially diagnosed with herpetic keratitis receiving full antiviral and corticosteroid topical treatment without any improvement. Corneal biopsy was performed to confirm the suspected diagnosis, and Acanthamoeba stromal cysts were identified in the sample. Treatment was initiated with 0.02% chlorhexidine, 0.1% propamidine isethionate, neomycin, and tropicamide/phenylephrine. Symptoms and clinical improvement were achieved between the 8th and 10th weeks, so corticosteroids were initiated. Treatment was continued until we observed a poor response in the left eye; therefore, an epithelial scraping and amniotic membrane placement were performed. Lately, the right eye underwent a deep anterior lamellar keratoplasty. A challenging case of bilateral AK managed with topical medications, amniotic membrane, and corneal keratoplasty. The earlier the disease is diagnosed, the better the outcome. If the diagnosis is delayed, the amoebas have penetrated deep into the corneal stroma, and successful therapy becomes difficult. A surgical option can be an early solution with a good prognosis for these cases.
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PURPOSE: The purpose of this double-masked, parallel randomised controlled trial was to compare the recurrence rate and other outcomes between conjunctival-limbal autograft (CLAu) and mini-simple limbal epithelial transplantation (mini-SLET) after excision of pterygium. METHODS: Eligibility criteria for participants was the presence of a primary nasal pterygium extending equally to or greater than two millimetres on the cornea on its horizontal axis from the nasal limbus. The participants were allocated into two groups (CLAu and mini-SLET) using simple randomisation with a table of random numbers. Participants and the outcome assessor were masked to the intervention. The study protocol is listed and available on https://clinicaltrials.gov (Identifier: NCT03363282). RESULTS: A total of 61 eyes were enrolled in the study, 33 underwent CLAu (group 1) and 28 mini-SLET (group 2), all eyes were analysed in each group. At 2, 3, 6 and 12 months the CLAu group exhibited a recurrence of 0%, 6.1%, 8.1% and 8.1%, while the mini-SLET exhibited a recurrence of 0%, 17.9%, 50% and 53.5% (p<0.05). There were no intraoperative or postoperative complications in either of the two groups. CONCLUSION: The findings of this study suggest that mini-SLET has a higher recurrence rate and provides no advantage over CLAu in the treatment of primary pterygium.
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Limbo da Córnea , Pterígio , Humanos , Pterígio/cirurgia , Autoenxertos , Túnica Conjuntiva/transplante , Transplante Autólogo , Limbo da Córnea/cirurgia , Recidiva , Resultado do Tratamento , SeguimentosRESUMO
Sargassum spp. flood the Caribbean coastline, causing damage to the local economy and environment. Anaerobic digestion (AD) has been proposed as an attractive option for turning macroalgae into valuable resources. Sargassum spp. has a complex composition that affects the microbial composition involved in AD which generates a low methane yield. This study aimed to improve the methane yield of pelagic Sargassum, using different energy-saving pretreatments and identifying the microbial community associated with methane production. We applied different energy-saving pretreatments to algal biomass and assessed the methane yield using a biomethane potential (BMP) test. The microbial communities involved in the AD of the best- and worst-performing methanogenic systems were analyzed by high-throughput sequencing. The results showed that pretreatment modified the content of inorganic compounds, fibers, and the C:N ratio, which had a strong positive correlation with BMP. The water washing pretreatment resulted in the best methane yield, with an increase of 38%. DNA metabarcoding analysis revealed that the bacterial genera Marinilabiliaceae_uncultured, DMER64, Treponema, and Hydrogenispora, as well as the archaea genera Methanosarcina, RumEn_M2, Bathyarchaeia, and Methanomassiliicocus, dominated the microbial community with a high methane yield. This study is the first to demonstrate the microbial community structure involved in the AD of Sargassum spp. The pretreatments presented in this study can help overcome the limitations associated with methane yield.
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Microbiota , Sargassum , Animais , Código de Barras de DNA Taxonômico , Microbiota/genética , DNA , Metano , MethanosarcinaRESUMO
PURPOSE: The aim of this study was to report a case of ocular Mpox that responded favorably to treatment with topical interferon and oral doxycycline. METHODS: This is a case report of a previously healthy 24-year-old woman who developed a pustular rash, headache, fever, arthralgia, sore throat, and asthenia 3 weeks before attending to our clinic. Her main complaint at the moment of the visit was pain, photophobia, foreign body sensation, blurred vision, red eye, and discharge on the left eye. The slit-lamp examination of the left eye showed severe conjunctival hyperemia associated with tarsal follicles, 360 degrees ciliary injection, diffuse corneal epithelial edema with white linear epithelial infiltrates, pigmented and nonpigmented keratic precipitates, and two 1-mm peripheral corneal ulcers with white infiltrates, associated with positive fluorescein staining. Anterior chamber cellularity and flare were mildly present. RESULTS: Mpox with ocular manifestations diagnosis was confirmed by real-time quantitative reverse transcription polymerase chain reaction assay (qRT-PCR) testing; samples were taken from corneal, conjunctival, and nasopharynx swab as well as a skin scab. Topical interferon alpha 2b 1 MIU/mL every 6 hours for 1 month and oral doxycycline 100 mg BID were administered along with other medications with consequent decrease of inflammation and malaise symptoms 1 week later, associated with uncorrected visual acuity improvement. CONCLUSIONS: Alternative and efficacious treatment options for Mpox ocular manifestations are needed to prevent further disease progression and sequelae in countries with no access to the gold-standard therapy. Topical interferon alpha 2b and oral doxycycline have shown adequate response as shown with this patient.
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Mpox , Humanos , Feminino , Adulto Jovem , Adulto , Doxiciclina , Administração Tópica , Interferon alfa-2 , Interferon-alfaRESUMO
PURPOSE: To describe the ocular clinical characteristics of a group of Mexican patients with lamellar ichthyosis (LI) arising from TGM1 pathogenic variants. METHODS: Ophthalmological exploration, pedigree analysis and genetic screening were performed in patients with an established clinical diagnosis of lamellar ichthyosis from families located in a small community in the Southeast of Mexico. RESULTS: Nine patients with LI in five families were identified. There were six affected females. All patients (9/9) demonstrated eye lid abnormalities with eight patients showing lid margin abnormalities. Madarosis was present in only three individuals and corneal scarring was documented in two. All nine individuals carried biallelic TGM1 variants, either homozygously or as compound heterozygous. CONCLUSION: Ocular anomalies are common in individuals with TGM1-related LI. The occurrence of a variety of private or rare mutations hampers the identification of a genotype-phenotype correlation for ocular anomalies in this disorder.
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Ictiose Lamelar , Feminino , Humanos , Pálpebras , Ictiose Lamelar/genética , México , Mutação , Transglutaminases/genéticaRESUMO
BACKGROUND: Data on visual impairment (VI) in patients with diabetes are necessary in order to guide economic and human resources for reducing its prevalence. OBJECTIVE: To estimate the prevalence of diabetic retinopathy-related VI in patients with type 2 diabetes in a hospital-based setting. MATERIAL AND METHODS: Cross-sectional study carried out from 2014 to 2019 in an ophthalmology outpatient clinic. Any VI was defined as corrected pin-hole visual acuity in the better eye of ≥ 0.24 logMAR. The presence of diabetic retinopathy (DR), diabetic macular edema (DME) and cataract was evaluated. RESULTS: A total of 840 patients were included; median diabetes duration was 15 years. The prevalence of VI was 30%. DR was found in 62% of patients (30% had sight-threatening DR [STDR]), 17% had referable DME, and 3%, cataracts. The odds ratio for moderate or worse VI was 9.02 for STDR (p < 0.001), 5.89 for referable DME (p = 0.001), and 2.51 for cataract (p = 0.006). CONCLUSION: Thirty percent of participants had some degree of VI. Moderate or worse VI showed a strong association with STDR and referable DME.
ANTECEDENTES: Los datos sobre discapacidad visual (DV) en pacientes con diabetes son necesarios para orientar los recursos económicos y humanos que disminuyan su prevalencia. OBJETIVO: Estimar la prevalencia de DV relacionada con retinopatía diabética en pacientes con diabetes tipo 2 en un entorno hospitalario. MATERIAL Y MÉTODOS: Estudio transversal realizado de 2014 a 2019 en una consulta externa de oftalmología. Cualquier DV se definió como agudeza visual corregida con agujero estenopeico en el ojo con mejor visión (≥ 0.24 logMAR). Se evaluó la presencia de retinopatía diabética, edema macular diabético (EMD) y cataratas. RESULTADOS: Se incluyeron 840 pacientes; la mediana de duración de la diabetes fue de 15 años. La prevalencia de DV fue de 30 %. Se encontró retinopatía diabética en 62 % (30 % tenía retinopatía diabética que amenazaba la visión [RDAV]); 17 %, EMD y 3 %, cataratas. La razón de momios para DV moderada o de mayor gravedad fue de 9.02 para RDAV (p < 0.001), 5.89 para EMD referible (p = 0.001) y 2.51 para catarata (p = 0.006). CONCLUSIÓN: Treinta por ciento de los participantes tenía algún grado de DV. La DV moderada o de mayor gravedad mostró una fuerte asociación con RDAV y EMD referible.
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Catarata , Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Edema Macular , Humanos , Retinopatia Diabética/complicações , Retinopatia Diabética/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Edema Macular/epidemiologia , Edema Macular/etiologia , Estudos Transversais , Hospitais , Catarata/complicações , Catarata/epidemiologia , Transtornos da Visão/etiologia , Transtornos da Visão/complicaçõesRESUMO
Resumen Antecedentes: Los datos sobre discapacidad visual (DV) en pacientes con diabetes son necesarios para orientar los recursos económicos y humanos que disminuyan su prevalencia. Objetivo: Estimar la prevalencia de DV relacionada con retinopatía diabética en pacientes con diabetes tipo 2 en un entorno hospitalario. Material y métodos: Estudio transversal realizado de 2014 a 2019 en una consulta externa de oftalmología. Cualquier DV se definió como agudeza visual corregida con agujero estenopeico en el ojo con mejor visión (≥ 0.24 logMAR). Se evaluó la presencia de retinopatía diabética, edema macular diabético (EMD) y cataratas. Resultados: Se incluyeron 840 pacientes; la mediana de duración de la diabetes fue de 15 años. La prevalencia de DV fue de 30 %. Se encontró retinopatía diabética en 62 % (30 % tenía retinopatía diabética que amenazaba la visión [RDAV]); 17 %, EMD y 3 %, cataratas. La razón de momios para DV moderada o de mayor gravedad fue de 9.02 para RDAV (p < 0.001), 5.89 para EMD referible (p = 0.001) y 2.51 para catarata (p = 0.006). Conclusión: Treinta por ciento de los participantes tenía algún grado de DV. La DV moderada o de mayor gravedad mostró una fuerte asociación con RDAV y EMD referible.
Abstract Background: Data on visual impairment (VI) in patients with diabetes are necessary in order to guide economic and human resources for reducing its prevalence. Objective: To estimate the prevalence of diabetic retinopathy-related VI in patients with type 2 diabetes in a hospital-based setting. Material and methods: Cross-sectional study carried out from 2014 to 2019 in an ophthalmology outpatient clinic. Any VI was defined as corrected pin-hole visual acuity in the better eye of ≥ 0.24 logMAR. The presence of diabetic retinopathy (DR), diabetic macular edema (DME) and cataract was evaluated. Results: A total of 840 patients were included; median diabetes duration was 15 years. The prevalence of VI was 30 %. DR was found in 62 % of patients (30 % had sight-threatening DR [STDR]), 17 % had referable DME, and 3 %, cataracts. The odds ratio for moderate or worse VI was 9.02 for STDR (p < 0.001), 5.89 for referable DME (p = 0.001), and 2.51 for cataract (p = 0.006). Conclusion: Thirty percent of participants had some degree of VI. Moderate or worse VI showed a strong association with STDR and referable DME.
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Purpose: To determine the effectiveness of subconjunctival application of a novel sirolimus liposomal formulation for the treatment of dry eye. Methods: A randomized, triple-blind, Phase II clinical trial. Thirty-eight eyes of 19 patients were included. Nine patients (18 eyes) assigned to the sham group (Sham) and 10 patients (20 eyes) to sirolimus-loaded liposomes group (Sirolimus). The treatment group received three doses of subconjunctival liposome-encapsulated sirolimus and the sham group received three doses of liposomal suspension without sirolimus. Subjective (Ocular Surface Disease Index, OSDI) and measured (corrected distance visual acuity, conjunctival hyperemia, tear osmolarity, Schirmer's test, corneal/conjunctival staining and matrix metalloproteinase-9) variables were measured. Results: Sirolimus-entrapped liposomes-treated group OSDI scores changed from 62.19 (± 6.07) to 37.8 (± 17.81) (p=0.0024), and conjunctival hyperemia from 2.0 (± 0.68) to 0.83 (± 0.61) (p<0.0001); Sham group with OSDI scores from 60.02 (± 14.2) to 36.02 (± 20.70) (p=0.01), and conjunctival hyperemia from 1.33 (± 0.68) to 0.94 (± 0.87) (p=0.048). All the other evaluated outcomes only showed significant differences in the sirolimus group: corneal/conjunctival staining score (p=0.0015), lipid layer interferometry (p=0.006), and inferior meibomian gland dropout (p=0.038). No local or systemic adverse effects regarding the medication itself were reported, and the administration route was well accepted. Conclusion: Our findings suggest that sub-conjunctival sirolimus-loaded liposomes are effective in reducing both signs and symptoms of dry eye in patients with poorly controlled moderate-to-severe DED, while avoiding other topical administration adverse effects. Further investigation with a larger sample size is required to determine long-term effects.